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Q99717

- SMAD5_HUMAN

UniProt

Q99717 - SMAD5_HUMAN

Protein

Mothers against decapentaplegic homolog 5

Gene

SMAD5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 155 (01 Oct 2014)
      Sequence version 1 (01 May 1997)
      Previous versions | rss
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    Functioni

    Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD).

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi65 – 651ZincBy similarity
    Metal bindingi110 – 1101ZincBy similarity
    Metal bindingi122 – 1221ZincBy similarity
    Metal bindingi127 – 1271ZincBy similarity

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. protein binding Source: UniProtKB
    3. receptor signaling protein activity Source: UniProtKB
    4. RNA polymerase II core promoter sequence-specific DNA binding Source: Ensembl
    5. sequence-specific DNA binding transcription factor activity Source: InterPro
    6. transforming growth factor beta receptor, pathway-specific cytoplasmic mediator activity Source: BHF-UCL
    7. ubiquitin protein ligase binding Source: BHF-UCL

    GO - Biological processi

    1. BMP signaling pathway Source: UniProtKB
    2. bone development Source: Ensembl
    3. cardiac muscle contraction Source: Ensembl
    4. cartilage development Source: Ensembl
    5. cellular response to BMP stimulus Source: BHF-UCL
    6. cellular response to organic cyclic compound Source: Ensembl
    7. embryonic pattern specification Source: UniProtKB
    8. erythrocyte differentiation Source: Ensembl
    9. germ cell development Source: Ensembl
    10. intracellular signal transduction Source: GOC
    11. Mullerian duct regression Source: Ensembl
    12. osteoblast fate commitment Source: Ensembl
    13. positive regulation of osteoblast differentiation Source: Ensembl
    14. positive regulation of transcription, DNA-templated Source: UniProtKB
    15. positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: BHF-UCL
    16. protein phosphorylation Source: Ensembl
    17. signal transduction Source: UniProtKB
    18. transcription, DNA-templated Source: UniProtKB-KW
    19. transforming growth factor beta receptor signaling pathway Source: UniProtKB
    20. ureteric bud development Source: Ensembl

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    ReactomeiREACT_12034. Signaling by BMP.
    SignaLinkiQ99717.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Mothers against decapentaplegic homolog 5
    Short name:
    MAD homolog 5
    Short name:
    Mothers against DPP homolog 5
    Alternative name(s):
    JV5-1
    SMAD family member 5
    Short name:
    SMAD 5
    Short name:
    Smad5
    Short name:
    hSmad5
    Gene namesi
    Name:SMAD5
    Synonyms:MADH5
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Unplaced

    Organism-specific databases

    HGNCiHGNC:6771. SMAD5.

    Subcellular locationi

    Cytoplasm. Nucleus
    Note: Cytoplasmic in the absence of ligand. Migrates to the nucleus when complexed with SMAD4.

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. integral component of membrane Source: UniProtKB
    3. intracellular Source: UniProtKB
    4. nucleoplasm Source: Reactome
    5. nucleus Source: UniProtKB
    6. protein complex Source: MGI
    7. transcription factor complex Source: InterPro

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi419 – 4191G → S: Loss of phosphorylation. 1 Publication

    Organism-specific databases

    PharmGKBiPA30528.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed2 Publications
    Chaini2 – 465464Mothers against decapentaplegic homolog 5PRO_0000090865Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylthreonine2 Publications
    Modified residuei463 – 4631Phosphoserine1 PublicationPROSITE-ProRule annotation
    Modified residuei465 – 4651Phosphoserine1 PublicationPROSITE-ProRule annotation

    Post-translational modificationi

    Phosphorylated on serine by BMP (bone morphogenetic proteins) type 1 receptor kinase.1 Publication
    Ubiquitin-mediated proteolysis by SMAD-specific E3 ubiquitin ligase SMURF1.

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ99717.
    PaxDbiQ99717.
    PRIDEiQ99717.

    PTM databases

    PhosphoSiteiQ99717.

    Expressioni

    Tissue specificityi

    Ubiquitous.

    Gene expression databases

    ArrayExpressiQ99717.
    BgeeiQ99717.
    CleanExiHS_SMAD5.
    GenevestigatoriQ99717.

    Organism-specific databases

    HPAiHPA058931.

    Interactioni

    Subunit structurei

    May form trimers with the co-SMAD SMAD4. Interacts with PEBP2-alpha subunit and SMURF1. Interacts with SUV39H1 and SUV39H2. Interacts (via MH2 domain) with LEMD3. Interacts with WWP1.2 Publications

    Protein-protein interaction databases

    BioGridi110265. 57 interactions.
    DIPiDIP-57571N.
    IntActiQ99717. 28 interactions.
    MINTiMINT-1180224.
    STRINGi9606.ENSP00000384803.

    Structurei

    3D structure databases

    ProteinModelPortaliQ99717.
    SMRiQ99717. Positions 10-133, 270-453.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini13 – 137125MH1PROSITE-ProRule annotationAdd
    BLAST
    Domaini271 – 465195MH2PROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi40 – 467Poly-Lys

    Sequence similaritiesi

    Belongs to the dwarfin/SMAD family.Curated
    Contains 1 MH1 (MAD homology 1) domain.PROSITE-ProRule annotation
    Contains 1 MH2 (MAD homology 2) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG330956.
    HOVERGENiHBG053353.
    InParanoidiQ99717.
    KOiK16790.
    PhylomeDBiQ99717.

    Family and domain databases

    Gene3Di2.60.200.10. 1 hit.
    3.90.520.10. 1 hit.
    InterProiIPR013790. Dwarfin.
    IPR003619. MAD_homology1_Dwarfin-type.
    IPR013019. MAD_homology_MH1.
    IPR017855. SMAD_dom-like.
    IPR001132. SMAD_dom_Dwarfin-type.
    IPR008984. SMAD_FHA_domain.
    [Graphical view]
    PANTHERiPTHR13703. PTHR13703. 1 hit.
    PfamiPF03165. MH1. 1 hit.
    PF03166. MH2. 1 hit.
    [Graphical view]
    SMARTiSM00523. DWA. 1 hit.
    SM00524. DWB. 1 hit.
    [Graphical view]
    SUPFAMiSSF49879. SSF49879. 1 hit.
    SSF56366. SSF56366. 1 hit.
    PROSITEiPS51075. MH1. 1 hit.
    PS51076. MH2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q99717-1 [UniParc]FASTAAdd to Basket

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    MTSMASLFSF TSPAVKRLLG WKQGDEEEKW AEKAVDALVK KLKKKKGAME    50
    ELEKALSSPG QPSKCVTIPR SLDGRLQVSH RKGLPHVIYC RVWRWPDLQS 100
    HHELKPLDIC EFPFGSKQKE VCINPYHYKR VESPVLPPVL VPRHNEFNPQ 150
    HSLLVQFRNL SHNEPHMPQN ATFPDSFHQP NNTPFPLSPN SPYPPSPASS 200
    TYPNSPASSG PGSPFQLPAD TPPPAYMPPD DQMGQDNSQP MDTSNNMIPQ 250
    IMPSISSRDV QPVAYEEPKH WCSIVYYELN NRVGEAFHAS STSVLVDGFT 300
    DPSNNKSRFC LGLLSNVNRN STIENTRRHI GKGVHLYYVG GEVYAECLSD 350
    SSIFVQSRNC NFHHGFHPTT VCKIPSSCSL KIFNNQEFAQ LLAQSVNHGF 400
    EAVYELTKMC TIRMSFVKGW GAEYHRQDVT STPCWIEIHL HGPLQWLDKV 450
    LTQMGSPLNP ISSVS 465
    Length:465
    Mass (Da):52,258
    Last modified:May 1, 1997 - v1
    Checksum:i4A1FD7EC7BD06728
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti175 – 1751D → H in AAC50791. (PubMed:8673135)Curated
    Sequence conflicti237 – 2371N → P in AAC50791. (PubMed:8673135)Curated
    Sequence conflicti293 – 2931S → R in AAC50791. (PubMed:8673135)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U59913 mRNA. Translation: AAC50791.1.
    AF010601 mRNA. Translation: AAB66353.1.
    AF010607
    , AF010602, AF010603, AF010604, AF010605, AF010606 Genomic DNA. Translation: AAB92396.1.
    U73825 mRNA. Translation: AAB95090.1.
    AF009744
    , AF009739, AF009740, AF009741, AF009742, AF009743 Genomic DNA. Translation: AAB82655.1.
    AF009678 mRNA. Translation: AAB72180.1.
    BC009682 mRNA. Translation: AAH09682.1.
    RefSeqiNP_001001419.1. NM_001001419.2.
    NP_001001420.1. NM_001001420.2.
    NP_005894.3. NM_005903.6.
    UniGeneiHs.167700.

    Genome annotation databases

    GeneIDi4090.
    KEGGihsa:4090.
    UCSCiuc003lbj.1. human.

    Polymorphism databases

    DMDMi13959566.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U59913 mRNA. Translation: AAC50791.1 .
    AF010601 mRNA. Translation: AAB66353.1 .
    AF010607
    , AF010602 , AF010603 , AF010604 , AF010605 , AF010606 Genomic DNA. Translation: AAB92396.1 .
    U73825 mRNA. Translation: AAB95090.1 .
    AF009744
    , AF009739 , AF009740 , AF009741 , AF009742 , AF009743 Genomic DNA. Translation: AAB82655.1 .
    AF009678 mRNA. Translation: AAB72180.1 .
    BC009682 mRNA. Translation: AAH09682.1 .
    RefSeqi NP_001001419.1. NM_001001419.2.
    NP_001001420.1. NM_001001420.2.
    NP_005894.3. NM_005903.6.
    UniGenei Hs.167700.

    3D structure databases

    ProteinModelPortali Q99717.
    SMRi Q99717. Positions 10-133, 270-453.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110265. 57 interactions.
    DIPi DIP-57571N.
    IntActi Q99717. 28 interactions.
    MINTi MINT-1180224.
    STRINGi 9606.ENSP00000384803.

    PTM databases

    PhosphoSitei Q99717.

    Polymorphism databases

    DMDMi 13959566.

    Proteomic databases

    MaxQBi Q99717.
    PaxDbi Q99717.
    PRIDEi Q99717.

    Protocols and materials databases

    DNASUi 4090.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 4090.
    KEGGi hsa:4090.
    UCSCi uc003lbj.1. human.

    Organism-specific databases

    CTDi 4090.
    GeneCardsi GC05P135496.
    HGNCi HGNC:6771. SMAD5.
    HPAi HPA058931.
    MIMi 603110. gene.
    neXtProti NX_Q99717.
    PharmGKBi PA30528.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG330956.
    HOVERGENi HBG053353.
    InParanoidi Q99717.
    KOi K16790.
    PhylomeDBi Q99717.

    Enzyme and pathway databases

    Reactomei REACT_12034. Signaling by BMP.
    SignaLinki Q99717.

    Miscellaneous databases

    GeneWikii Mothers_against_decapentaplegic_homolog_5.
    GenomeRNAii 4090.
    NextBioi 16034.
    PROi Q99717.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q99717.
    Bgeei Q99717.
    CleanExi HS_SMAD5.
    Genevestigatori Q99717.

    Family and domain databases

    Gene3Di 2.60.200.10. 1 hit.
    3.90.520.10. 1 hit.
    InterProi IPR013790. Dwarfin.
    IPR003619. MAD_homology1_Dwarfin-type.
    IPR013019. MAD_homology_MH1.
    IPR017855. SMAD_dom-like.
    IPR001132. SMAD_dom_Dwarfin-type.
    IPR008984. SMAD_FHA_domain.
    [Graphical view ]
    PANTHERi PTHR13703. PTHR13703. 1 hit.
    Pfami PF03165. MH1. 1 hit.
    PF03166. MH2. 1 hit.
    [Graphical view ]
    SMARTi SM00523. DWA. 1 hit.
    SM00524. DWB. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49879. SSF49879. 1 hit.
    SSF56366. SSF56366. 1 hit.
    PROSITEi PS51075. MH1. 1 hit.
    PS51076. MH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Localization of SMAD5 and its evaluation as a candidate myeloid tumor suppressor."
      Hejlik D.P., Kottickal L.V., Liang H., Fairman J., Davis T., Janecki T., Sexton D., Perry W. III, Tavtigian S.V., Teng D.H., Nagarajan L.
      Cancer Res. 57:3779-3783(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    3. "Smad5, a tumor suppressor candidate at 5q31.1, is hemizygously lost and not mutated in the retained allele in human leukemia cell line HL60."
      Zavadil J., Brezinova J., Svoboda P., Zemanova Z., Michalova K.
      Leukemia 11:1187-1192(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "hSmad5 gene, a human hSmad family member: its full length cDNA, genomic structure, promoter region and mutation analysis in human tumors."
      Gemma A., Hagiwara K., Vincent F., Ke Y., Hancock A.R., Nagashima M., Bennett W.P., Harris C.C.
      Oncogene 16:951-956(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    5. "Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12."
      Nishimura R., Kato Y., Chen D., Harris S.E., Mundy G.R., Yoneda T.
      J. Biol. Chem. 273:1872-1879(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF GLY-419.
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Uterus.
    7. Bienvenut W.V., Lempens A., Norman J.C.
      Submitted (OCT-2009) to UniProtKB
      Cited for: PROTEIN SEQUENCE OF 2-16; 34-40; 130-158; 283-306 AND 309-319, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY.
      Tissue: Ovarian carcinoma.
    8. Cited for: REVIEW.
    9. "Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells."
      Verschueren K., Huylebroeck D.
      Cytokine Growth Factor Rev. 10:187-199(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    10. Cited for: REVIEW.
    11. Cited for: REVIEW.
    12. "Suv39h histone methyltransferases interact with Smads and cooperate in BMP-induced repression."
      Frontelo P., Leader J.E., Yoo N., Potocki A.C., Crawford M., Kulik M., Lechleider R.J.
      Oncogene 23:5242-5251(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SUV39H1 AND SUV39H2.
    13. "The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines."
      Pan D., Estevez-Salmeron L.D., Stroschein S.L., Zhu X., He J., Zhou S., Luo K.
      J. Biol. Chem. 280:15992-16001(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LEMD3.
    14. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    16. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    17. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463 AND SER-465, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    19. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
      Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
      Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    20. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiSMAD5_HUMAN
    AccessioniPrimary (citable) accession number: Q99717
    Secondary accession number(s): O14688, Q15798, Q9UQA1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 4, 2001
    Last sequence update: May 1, 1997
    Last modified: October 1, 2014
    This is version 155 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3